Exploration of Chemokine Receptor 4 Targeted [68Ga]Ga-pentixafor PET/CT in Radioiodine-refractory Differentiated Thyroid Cancer.

PURPOSE: This study compared the diagnostic performance of [18F]FDG and [68Ga]Ga-Pentixafor PET/CT in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and assessed clinicopathological characteristics and uptake parameters. METHODS: Participants with RAIR-DTC were prospectively enrolled and underwent both [18F]FDG PET/CT and [68Ga]Ga-Pentixafor PET/CT within two weeks. Images were visually and semi-quantitatively analyzed, with lesion number, location, and uptake parameters recorded. The diagnostic performance of the two tracers was compared, and correlations of uptake parameters with clinicopathological characteristics were further evaluated. RESULTS: Nineteen patients with RAIR-DTC (median age, 60 years) were analyzed. A total of 125 lesions were identified, with 92.8% detected on [18F]FDG and 89.6% on [68Ga]Ga-Pentixafor (P = 0.289). Overall, [18F]FDG demonstrated higher median SUVmax, tumor-to-background ratio (TBR), and tumor-to-bone marrow ratio (TMR) than [68Ga]Ga-Pentixafor (7.33 vs. 3.03; 9.04 vs. 3.11; 4.88 vs. 1.96, respectively; all P < 0.001), while 31.4% (37/118) of lesions detected by at least one tracer showed higher [68Ga]Ga-Pentixafor uptake than [18F]FDG (median SUVmax 4.10 vs. 2.63). Among Pentixafor-positive confirmed lesions, 72.3% had TMR > 1 and 31.3% had TMR > 2. No significant clinicopathological associations with PET parameters were observed. CONCLUSION: [68Ga]Ga-Pentixafor PET/CT showed no significant difference in lesion detection compared with [18F]FDG in this RAIR-DTC cohort. Despite lower overall uptake than FDG, one-third of lesions showed higher [68Ga]Ga-Pentixafor uptake, and approximately one-third of Pentixafor-positive lesions exhibited TMR greater than two, suggesting that TMR may be an exploratory imaging marker warranting validation for CXCR4-targeted therapy selection.